Researchers at the NIH have uncovered why GLP-1 drugs like Ozempic and Wegovy lose their weight-loss punch over time. Using fluorescence imaging in mice, scientists tracked how semaglutide affects appetite-controlling brain cells in the area postrema. They found that the drug raises levels of a signaling molecule called cAMP, but not equally in every neuron. Some cells sustain high cAMP levels longer, while others drop off quickly — possibly because they break down or absorb the drug's receptors. When researchers blocked an enzyme called PDE4 using a drug called roflumilast, more neurons held onto elevated cAMP signals for longer. This finding suggests a potential strategy to help people push past weight-loss plateaus and possibly reduce how often injections are needed.
